The authors have no conflict of interest.
NF-κB p50 and p52 Expression Is Not Required for RANK-Expressing Osteoclast Progenitor Formation but Is Essential for RANK- and Cytokine-Mediated Osteoclastogenesis†
Article first published online: 1 JUL 2002
Copyright © 2002 ASBMR
Journal of Bone and Mineral Research
Volume 17, Issue 7, pages 1200–1210, July 2002
How to Cite
Xing, L., Bushnell, T. P., Carlson, L., Tai, Z., Tondravi, M., Siebenlist, U., Young, F. and Boyce, B. F. (2002), NF-κB p50 and p52 Expression Is Not Required for RANK-Expressing Osteoclast Progenitor Formation but Is Essential for RANK- and Cytokine-Mediated Osteoclastogenesis. J Bone Miner Res, 17: 1200–1210. doi: 10.1359/jbmr.2002.17.7.1200
- Issue published online: 2 DEC 2009
- Article first published online: 1 JUL 2002
- Manuscript Accepted: 21 DEC 2001
- Manuscript Revised: 4 DEC 2001
- Manuscript Received: 16 SEP 2001
Expression of RANKL by stromal cells and of RANK and both NF-κB p50 and p52 by osteoclast precursors is essential for osteoclast formation. To examine further the role of RANKL, RANK, and NF-κB signaling in this process, we used NF-κB p50−/−;p52−/− double knockout (dKO) and wild-type (WT) mice. Osteoclasts formed in cocultures of WT osteoblasts with splenocytes from WT mice but not from dKO mice, a finding unchanged by addition of RANKL and macrophage colony-stimulating factor (M-CSF). NF-κB dKO splenocytes formed more colony-forming unit granulocyte macrophage (CFU-GM) colonies than WT cells, but no osteoclasts were formed from dKO CFU-GM colonies. RANKL increased the number of CFU-GM colonies twofold in WT cultures but not in dKO cultures. Fluorescence-activated cell sorting (FACS) analysis of splenocytes from NF-κB dKO mice revealed a two-to threefold increase in the percentage of CD11b (Mac-1) and RANK double-positive cells compared with WT controls. Treatment of NF-κB dKO splenocytes with interleukin (IL)-1, TNF-α, M-CSF, GM-CSF, and IL-6 plus soluble IL-6 receptor did not rescue the osteoclast defect. No increase in apoptosis was observed in cells of the osteoclast lineage in NF-κB dKO or p50−/−;p52+/− (3/4KO) mice. Thus, NF-κB p50 and p52 expression is not required for formation of RANK-expressing osteoclast progenitors but is essential for RANK-expressing osteoclast precursors to differentiate into TRAP+ osteoclasts in response to RANKL and other osteoclastogenic cytokines.